Feeding elicited by benzodiazepine-like chemicals in puppies and cats: Structure-activity relationships

Abstract

To assess the relationship between the structure of benzodiazepines and their activity as feed intake stimulants, benzodiazepines of different structural subclasses were given per os as a drench to puppies and young cats. The chemicals included diazepam (D), elfazepam (E), a 1,5 benzodiazepine (WE405), a triazolobenzodiazepine (U31889), a l-pyridyl triazolobenzodiazepine (U37576), and a thienotriazolodiazepine (WE941). Although all chemicals increased feed intake, there were definite structure-activity differences as well as differences in sensitivity between the cats and puppies. In the puppies, U37576 was the most potent chemical (least chemical required), while E elicited greater feeding responses compared with U37576. In the cats E also stimulated the most feeding, but WE941 and U31889 were the most potent chemicals. WE405 was the least effective chemical in puppies but worked well as a stimulant of 24-hr feed intake in cats. The cats were approximately 2 (U37576) to 7 (D) times more sensitive (mg/kg b.w.) than the dogs to the effects of the chemicals. Time patterns of feeding varied among the chemicals and in general were similar for both puppies and cats. All the chemicals except E caused some degree of either ataxia or excitement in both puppies and cats. Thus, based on its effectiveness as a feed intake stimulant, as well as its lack of undesirable side effects, E is proposed to be most useful therapeutically as an oral feed intake stimulant for these species.